PROJECT SUMMARY CORE B: BEHAVIORAL PHENOTYPING The Behavioral Phenotyping Core will be responsible for integrating behavioral testing protocols and executing multidimensional phenotyping batteries in support of the Center for Systems Neurogenetics of Addiction (CSNA). The Mouse Neurobehavioral Phenotyping Facility (MNBF) at The Jackson Laboratory is a dedicated behavioral testing facility optimized for conducting sensitive studies in laboratory mice with a mission to provide investigators the resources and expertise required to conduct comprehensive and complex neurobehavioral testing. As a research core, the MNBF is well-positioned with its existing infrastructure to support large-scale characterization of behavioral phenotypes relevant to the genetic underpinnings of addiction. In the proposed Center, the MNBF will provide advanced behavioral phenotyping capabilities and instrumentation in close proximity to mouse resources, along with dedicated staff proficient in conducting these procedures and highly trained in behavioral testing of mice of various inbred strains and the heterogeneous, highly diverse outbred mouse populations. In addition to the execution of experiments, the Core will support interpretation of complex behaviors, contribute to biobanking efforts, maintain and provide access to testing protocols, data pre- processing and transfer through the LIMS system to the IGGC for a publicly available data repository in close coordination with the Integrative Genetics and Genomics Core. A critical challenge for many investigators wishing to employ mouse genetics research, particularly in heterogeneous and diverse mouse populations, is the scale and complexity of experimentation as well as the critical requirements of expertise, particularly in behavioral testing. We propose three Specific Aims: Aim 1: We will validate complex behavioral tests relevant to addiction-related behaviors; integrating them into a multidimensional phenotyping battery. The Core will adopt protocols from the CSNA project leaders and demonstrate through cross-laboratory assay validation the utility, robustness, reliability, and the ability to integrate the testing paradigms into a multidimensional testing battery. This aim will also support the demonstration of the proficiency of staff to execute complex testing batteries and also help to inform assay throughput as well as inter-strain variability. Aim 2: We will perform the behavioral characterization of diverse genetic, heterogeneous mouse populations (i.e., Collaborative Cross, DO strains) through the multidimensional phenotyping batteries in support of the CSNA research projects. Following assay validation, as defined by the ability to reproduce data in select founder strains as published by the CSNA project leaders, we will focus on applying the expertise of trained staff to execute the integrated testing batteries on these mouse populations under the guidance of the CSNA project leaders. Aim 3: We will provide external investigators with in-depth characterization of addiction candidate genes using the broad- based phenotyping capabilities of the Center. The Core will provide these investigators with access to facilities, expertise, and training to extend behavioral characterization of candidate genes or provide comprehensive behavioral characterization of novel mutant mice to assess behavioral phenotypes relevant to both addiction- related behaviors and related co-morbidities such as anxiety, depression, cognition, and social behavior. In addition, other behavioral phenotypes that confound the interpretation of the primary behavioral endpoints may also be evaluated.